Maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA1/2 mutati...

Date 21 October 2018
Event ESMO 2018 Congress
Session Presidential Symposium 2
Topics Ovarian Cancer
Anticancer Agents
Personalised/Precision Medicine
Presenter Kathleen Moore
Authors K.N. Moore1, N. Colombo2, G. Scambia3, B. Kim4, A. Oaknin5, M. Friedlander6, A. Lisyanskaya7, A. Floquet8, A. Leary9, G.S. Sonke10, C. Gourley11, S. Banerjee12, A.M. Oza13, A. González-Martín14, C. Aghajanian15, W. Bradley16, E.S. Lowe17, R. Bloomfield18, P. DiSilvestro19
  • 1,, Stephenson Oklahoma Cancer Center, 73104 - Oklahoma City/US
  • 2,, University of Milan-Bicocca and Istituto Europeo di Oncologia, 20141 - Milan/IT
  • 3,, Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, 00168 - Roma/IT
  • 4,, Samsung Medical Center, Sungkyunkwan University School of Medicine, 135710 - Seoul/KR
  • 5,, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 6,, University of New South Wales Clinical School, Prince of Wales Hospital, 2031 - Randwick/AU
  • 7,, St Petersburg City Oncology Dispensary, St Petersburg/RU
  • 8,, Institute Bergonié, Comprehensive Cancer Centre, 33076 - Bordeaux/FR
  • 9,, Gustave-Roussy Cancer Campus, 94800 - Villejuif/FR
  • 10,, The Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
  • 11,, Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XR - Edinburgh/GB
  • 12,, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, SW3 6JJ - London/GB
  • 13,, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 14,, Clínica Universidad de Navarra, Madrid/ES
  • 15,, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 16,, Froedtert and the Medical College of Wisconsin, Milwaukee/US
  • 17,, AstraZeneca, Gaithersburg/US
  • 18,, AstraZeneca, Cambridge/GB
  • 19,, Women and Infants Hospital, Providence/US

Abstract

Background

Pts with newly diagnosed advanced OC are treated with cytoreductive surgery and platinum-based chemotherapy. Most relapse within the first 3 years and have further chemotherapy, but once relapsed are largely not curable. SOLO1 (NCT01844986) is the first Phase III trial to evaluate PARP inhibitor (olaparib [Lynparza®]) maintenance therapy after platinum-based chemotherapy in newly diagnosed advanced OC with a BRCAm.

Methods

SOLO1 is a randomized, controlled, double-blind trial. Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid ovarian, primary peritoneal and/or fallopian tube cancer with a BRCAm, had received platinum-based chemotherapy and were in clinical complete or partial response. Pts were randomized 2:1 to olaparib tablets 300 mg bd or placebo. The primary endpoint was investigator-assessed progression-free survival (PFS; modified RECIST v1.1).

Results

Of 391 randomized pts, 260 received olaparib and 130 placebo (one pt did not receive placebo). Median follow-up was 41 months. Baseline characteristics were well balanced. Primary PFS analysis showed a significant 70% reduction in the risk of progression or death with olaparib versus placebo (Table). PFS sensitivity analyses, second PFS and time to first subsequent therapy or death support the primary analysis. Overall survival data are immature.

Median, months HR (95% CI)
P value
Olaparib
(N=260)
Placebo
(N=131)
Between-group
difference
PFS, investigator
assessed
(51% maturity)
NR 13.8 NC 0.30 (0.23–0.41)
P<0.0001
PFS, BICR*
(38% maturity)
NR 14.1 NC 0.28 (0.20–0.39)
P<0.0001
TFST 51.8 15.1 36.7 0.30 (0.22–0.40)
P<0.0001
PFS2
(31% maturity)
NR 41.9 NC 0.50 (0.35–0.72)
P=0.0002
*Sensitivity analysis using BICR
BICR, blinded independent central review; HR, hazard ratio; NC, not calculable; NR, not reached; PFS, progression-free survival; PFS2, time from randomization to second progression or death; TFST, time to first subsequent therapy or death

Adverse events were mostly low grade. The most common grade ≥3 toxicities with olaparib were anaemia (22%) and neutropenia (8%). Olaparib dose reductions, interruptions and discontinuations occurred in 28%, 52% and 12%, respectively. There was no change from baseline in health-related quality of life scores with olaparib.

Conclusions

Maintenance olaparib led to a substantial, unprecedented improvement in PFS, with an estimated difference in median PFS for olaparib versus placebo of approximately 3 years.

Clinical trial identification

ClinicalTrials.gov NCT01844986, July 2018

Editorial Acknowledgement

Editorial assistance was provided by Gillian Keating, Mudskipper Business Limited, funded by AstraZeneca and Merck & Co., Inc..